The overall goal of this project is to characterize the nature and extent of abnormalities in phospholipid (PL) metabolism that are associated with neuronal dysfunction and degeneration in Alzheimer's disease (AD). It is hypothesized that abnormalities in the metabolism of phosphatidylcholine (PC) and possibly other PLs are associated specifically with neuronal dysfunction and degeneration in AD and are distinct from findings in other neurodegenerative diseases or changes that may occur during normal aging. In order to test this hypothesis, we will measure levels of PLs and water-soluble precursors and metabolites of PC and other PLs in brain tissue obtained at autopsy from patients with AD, Huntington's disease, and from two groups of control subjects: one with ages between 20 and 40, and the second with ages between 60 and 80 years old. Brain samples will be from frontal, temporal, and occipital cortex; hippocampus; and the caudate nucleus and ventral forebrain CH 1-4 nuclear region. The proposed research takes advantage of resources in the Massachusetts ADRC, including the Tissue Resource Center of the Neuropathology Core and biostatistical expertise in the Administrative Core. Identification of characteristic abnormalities in the PL metabolism in brains of patients with AD may provide new explanations for neuronal dysfunction and death.